Why Personalized Cancer Immunotherapy?

Advances in genomic sequencing and bioinformatics over the past decade have presented a clearer understanding, at the molecular level, of the challenges to the immune response to cancer. In fact, during this decade of enlightenment, the development of better sequencing and laboratory tools has expanded our knowledge and capabilities of the neoantigens derived from somatic mutations produced in the repertoire of tumor cells. The summarized current results estimate millions of coding region mutations in Adenocarcinoma tumors and estimate drug resistance to be 1 in 5000 tumor cells of any individual clone.  Assuming that this is 12 to 13 cell divisions with the established somatic cell doubling time of 6 hours, that could be a loss of potential immune targets every 3 to 4 days. This off-target condition is a limitation of all forms of systemic drugs, passive antibodies as well as active immunotherapy, and does not bode well for the “targeted therapy” approach. My good friend and colleague, the late Dr. I. J. Fidler, points out first, targeted therapy requires a stable target. Second, heterogeneous disease cannot be treated by a homogeneous therapy. Third, a chronic disease cannot be treated acutely. Serious consideration of these principles allow the designing of better immunotherapies for the fatal phase of cancer metastasis.” It is no longer logical to treat a heterogeneous disease with a homogeneous treatment.

With lessons learned from the preclinical studies in the Line 10 syngeneic guinea pig model, we conducted active specific immunotherapy of occult disease and achieved major clinical success in Stage II (T3 & T4a, b) colon cancer, an unmet medical need.  We have performed clinical studies with a patient specific vaccine, performed in hundreds of colon cancer patients.  This programmed approach has been shown in clinical trials to possess the 4 P’s necessary for patient specific active immunotherapy, Personalized, Precision, Potency, and Prevention of post-surgical occult disease.